Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation.

Jiaqi Yu, Yuanfeng Fu, Weifeng Xu, Ren-Bo Ding, Jiaolin Bao
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Abstract

Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.

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化疗诱发神经病变的发病机理和治疗方法透视:关注氧化应激和神经炎症。
癌症是一种全球流行的高发病。化疗是治疗癌症的主要方法,但它也会带来严重的副作用。化疗引起的周围神经病(CIPN)和化疗引起的认知障碍(CICI)是化疗中出现的两种主要并发症。它们都与神经系统损伤有关,因此统称为化疗诱发神经病(CIN)。化疗诱发神经病变会引起神经痛和肢体麻木,而化疗诱发神经病变则会导致失忆和认知功能障碍。目前,还没有有效的疗法来预防或治疗 CIN,因此研究缓解 CIN 的新药已迫在眉睫。氧化应激和神经炎症是 CIPN 和 CICI 的共同致病机制。过量的活性氧(ROS)和促炎细胞因子会导致外周神经系统损伤,从而引起 CIPN。外周活性氧和细胞因子还会改变血脑屏障的通透性,从而增加中枢神经系统的氧化应激和神经炎症,最终导致 CICI。一些抗抑郁药物已被用于治疗 CIN,并取得了良好的临床效果。据报道,这些药物的潜在药理机制是改善氧化应激和神经炎症,为有效治疗 CIN 指引了一条新的可行之路。这篇微型综述总结了 CIN 研究在临床现状、发病机制和治疗方面的最新进展。它还探讨了将抗抑郁药重新用于 CIN 治疗的潜力,并展望了针对氧化应激和神经炎症开发 CIN 治疗药物的策略。
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来源期刊
CiteScore
4.80
自引率
9.10%
发文量
55
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